Losartan Inhibits Vascular Smooth Muscle Cell Proliferation through Activation of AMP-Activated Protein Kinase.
10.4196/kjpp.2010.14.5.299
- Author:
Jung Eun KIM
1
;
Hyoung Chul CHOI
Author Information
1. Department of Pharmacology, Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717, Korea. hcchoi@med.yu.ac.kr
- Publication Type:Original Article
- Keywords:
AMP-activated protein kinase (AMPK);
Angiotensin II type 1 (AT1) receptor antagonist;
Losartan;
Vascular smooth muscle cells (VSMCs);
Proliferation
- MeSH:
Acetyl-CoA Carboxylase;
AMP-Activated Protein Kinases;
Angiotensin II;
Blotting, Western;
Cell Cycle;
Cell Cycle Checkpoints;
Cell Proliferation;
Contracts;
Cyclin D;
Cyclin E;
Cyclins;
Losartan;
Muscle, Smooth, Vascular;
Phosphorylation;
Proteins;
RNA, Small Interfering
- From:The Korean Journal of Physiology and Pharmacology
2010;14(5):299-304
- CountryRepublic of Korea
- Language:English
-
Abstract:
Losartan is a selective angiotensin II (Ang II) type 1 (AT1) receptor antagonist which inhibits vascular smooth muscle cells (VSMCs) contraction and proliferation. We hypothesized that losartan may prevent cell proliferation by activating AMP-activated protein kinase (AMPK) in VSMCs. VSMCs were treated with various concentrations of losartan. AMPK activation was measured by Western blot analysis and cell proliferation was measured by MTT assay and flowcytometry. Losartan dose- and time-dependently increased the phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase (ACC) in VSMCs. Losartan also significantly decreased the Ang II- or 15% FBS-induced VSMC proliferation by inhibiting the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. Compound C, a specific inhibitor of AMPK, or AMPK siRNA blocked the losartan-induced inhibition of cell proliferation and the G0/G1 cell cycle arrest. These data suggest that losartan-induced AMPK activation might attenuate Ang II-induced VSMC proliferation through the inhibition of cell cycle progression.
